1.
A normally hydrated healthy 24‐year‐old male volunteer takes a maximal dose of desmopressin ( a long lasting form of Arginine vasopressin: ADH) by nasal spray. What will be the resultant change in osmolarity of tubular fluid in the nephron segments listed in the table?
Correct Answer
D. 4
Explanation
Vasopressin V2 receptors are located on the basolateral membranes of cells of the cortical, outer medullary and inner medullary collecting ducts. The major physiological role of ADH is to control water and urea permeability in the collecting duct system thereby mediating urine concentration and dilution. Remember that fluid at the end of the proximal tubule is isotonic with blood plasma, but then becomes progressively more concentrated as the fluid flows towards the hairpin turn of Henle's loop. It is then diluted in the ascending limb so that it is hypotonic when it returns to the distal tubule. In the absence of ADH, tubular fluid remains hypotonic from the distal tubule throughout the collecting duct system, because the water permeability of the collecting duct system is low, and despite a strong osmotic gradient favoring water absorption, water cannot equilibrate across the collecting duct epithelium. In the presence of ADH, the water permeability of the collecting duct system is increased greatly. This allows osmotic equilibration between the fluid in the lumen and the interstitium, so the osmotic pressure of fluid in the collecting duct system will be increased to match the osmotic pressure of the medullary interstitium. ADH also increases the permeability of the inner medullary collecting duct to urea, which is reabsorbed more efficiently. This increases the osmotic pressure in the medulla ‐ contributing to the osmotic gradient in the inner medulla. This means that fluid in the loop of Henle will reach a higher osmotic pressure at all levels. The fluid still becomes diluted in the ascending limb, but less so than in the absence of ADH. Therefore the osmotic pressure of fluid in the distal convoluted tubule is also increased. See slides 20 and 21 of the concentration and dilution lecture. For further reading see Chapter 6 of "Vander's Renal Physiology"
2.
An experiment was performed measuring the net rates of water movement across a piece of human small intestine. Under normal conditions, the net rate was positive ‐ indicating water was absorbed. In the presence of cholera toxin, the net rate of movement became negative. Which is the principal mechanism by which the effect of the cholera toxin caused the change in the net direction of fluid movement?
Correct Answer
C. Stimulation of electrogenic chloride secretion
Explanation
Cholera toxin binds to plasma membrane receptors which results in production of
intracellular cAMP. cAMP activates chloride secretion predominantly through CFTR channels.
This electrogenic secretion causes sodium ions and water to enter the lumen of the small
intestine resulting in net fluid secretion. In vivo the fluid loss can be alleviated by stimulating
electrogenic sodium glucose absorption (SGLT1) in the small intestine.
In the small intestine, sodium is also absorbed by electroneutral processes (Na/H exchange) ‐
which drives some water absorption. There is some evidence that these transporters are
inhibited by cholera toxin which does contribute to the loss of fluid. However, it is not the
principle mechanism by which cholera toxin causes diarrhea. Electrogenic potassium secretion
does not occur in the small intestine (potassium is reabsorbed there), it occurs in the distal
colon. Likewise, sodium‐dependent absorption of short chain fatty acids occurs predominantly
in the colon, not the small intestine.
See slides 18, 35, 36, 37, 39, 40 & 49 of small intestine lecture.
See Chapter 26 of Ganong's Review of Medical Physiology for further reading.
3.
A 27‐year‐old man reports that lately he has been feeling confused and is progressively
more lethargic and weak. Laboratory tests reveal:
Plasma osmolarity: below normal
Urine osmolarity: above normal
Urine output: below normal
Plasma ADH levels: above normal
Which of the following conditions is the patient likely to be suffering?
Correct Answer
A. Syndrome of Inappropriate ADH secretion (SIADH)
Explanation
person is most likely suffering from SIADH. Uncontrolled ADH secretion (e.g.
from a small cell carcinoma in the lung), will lead to increased plasma ADH levels, which
stimulates water absorption from the collecting duct, increasing urine osmolarity and reducing urine output. The elevated reabsorption of water dilutes the plasma leading to a decreased
plasma osmolarity.
A high plasma ADH level would also be expected in nephrogenic diabetes insipidus. However, in
nephrogenic diabetes insipidus, urine osmolarity would be decreased (not increased) and urine
output would be increased ‐ not decreased.
In central diabetes insipidus, ADH levels would be low and, because of the low plasma ADH,
urine output would rise (not fall) because water absorption from the collecting duct is reduced.
The urine osmolarity would therefore be low and not high. Increased renal loss of water would
cause plasma osmolarity to rise (not fall).
Polydipsia (increased water intake) would reduce ADH levels. Increased water intake dilutes the
plasma resulting in lowered plasma osmolarity ‐ which is the primary signal for suppression of
ADH release. This would lead to reduced water reabsorption by the collecting duct, increasing
urine output which would have reduced (not raised) osmolarity.
These conditions were not covered specifically in the lectures ‐ but if you understand the
concepts covered in the urine concentration and dilution lecture and the control of body fluid
volume and osmolarity, you should be able to reason through the physiology to arrive at the
correct answer. These conditions were covered in detail in the Endocrine block e.g. see slides 57
& 58 of Thomas & Wright "Hypothalamus & Pituitary".
If you would like to read around these topics see Chapter 7 of "Vander's Renal Physiology"
4.
An increase in Angiotensin II levels sufficient to increase GFR will result in an increased
reabsorption of sodium by the proximal tubule to preserve fractional excretion. Which of the
following will contribute to this process most significantly?
Correct Answer
C.
Explanation
The process of filtration of solutes and water leads to an increase in the oncotic
pressure of plasma entering the peritubular capillaries. This is a key factor in determining uptake
of reabsorbed solutes and water. Increased uptake into the peritubular capillaries reduces the
amount of passive back‐leak of solutes and water from the cortical interstitium into the tubular
lumen. An increase in filtration caused for example, by moderate efferent arteriolar constriction
raises the peritubular capillary oncotic pressure ‐ resulting in higher uptake of reabsorbed
solutes and water. This leads to reduced back‐leak and therefore an increase in the amount of
solutes and water reabsorbed. This coupling between filtration and reabsorption is known as
glomerulotubular balance.
Increased hydrostatic pressure in the peritubular capillaries would reduce reabsorption not
increase it.
An increased sodium concentration in the peritubular capillary plasma would increase uptake
because the driving force for sodium diffusion into the capillary would increase and this would
lead to greater uptake. However, since sodium is freely filtered, and is accompanied by an
osmotically equivalent amount of water, its concentration in the peritubular capillaries remains
the same.
Proximal tubular reabsorption is (9like other nephron segments) dependent on tubular flow rate,
but increased filtration would raise proximal tubular flow rate not decrease it.
See slides 14 & 15 of the Tubular Functions lecture.
For further reading on glomerulotubular balance see Chapter 7 of Vander's Renal Physiology
5.
Which of the following solutes becomes less concentrated by the end of the proximal
tubule?
Correct Answer
E. pHospHate
Explanation
Feedback: Phosphate is almost completely reabsorbed by the time the filtrate has reached the
end of the proximal tubule. The distal tubule contributes a small amount to normal phosphate
handling, so changes in urinary excretion result primarily from alterations in proximal tubular
handling.
Sodium is reabsorbed in osmotically equivalent amounts with water, so the concentration
hardly changes, chloride concentration increases due to preferential reabsorption of
bicarbonate in the early proximal tubule.
Creatinine is subject to secretion in the proximal tubule and filtered creatinine is not
reabsorbed, so its concentration also rises. Urea concentration also increases along the proximal
tubule, due to water reabsorption.
See slide 8 of Tubular function and 5 of Tubular functions 2
6.
As part of a clinical trial, a healthy female volunteer receives a drug that dilates the
afferent arteriole and constricts the efferent arteriole by the same amounts. Assuming these
are the only actions of the drug, what will be the effects on GFR, RBF, and filtration fraction?
Correct Answer
C. 3
Explanation
Total RBF will show no change because the drug has no effect on total renal vascular
resistance. GFR will increase because PGC increases and filtration fraction will, therefore, also
increase. Because filtration fraction increases, there will be a larger than average increase in
ΠGC in along glomerular capillaries, and this will offset some of the GFR‐increasing effect of the
increased PGC. Therefore, GFR will not increase as much proportionately as does the PGC
See slides 22, 23, 25 of Filtration and blood flow lecture. For further reading see Chapter 2 of
"Vander's Renal Physiology"
7.
A laboratory experiment investigating GI motility measured the tension developed in strips of gastrointestinal smooth muscle. A number of gastrointestinal peptides were tested for their effects on the tension of the strips. Which of the following peptides would have caused tension to fall?
Correct Answer
D. Vasoactive intestinal polypeptide
Explanation
Vasoactive intestinal polypeptide (VIP) is a GI "neurocrine" peptide that causes
relaxation of smooth muscle in all parts of the GI tract. It (with nitric oxide) mediates relaxation
of smooth muscle distal to a bolus of food ‐ allowing contraction (mediated by acetylcholine and
substance P) behind the bolus to propel the matter in an anal direction (peristalsis). For example,
VIP mediates the relaxation of the lower esophagus and slower esophageal sphincter (receptive
relaxation) that allows a swallowed bolus of food to enter the stomach.
Gastrin and CCK act via the same receptor (CCKB) in mediating their effects on smooth muscle
contractility ‐ which is to cause contraction not relaxation. CCK causes relaxation of the
Sphincter of Oddi indirectly through a reflex resulting in the release of VIP.
Secretin has no physiologically significant effect on motility ‐ it stimulates pancreatic secretion
predominantly of electrolytes (bicarbonate) and water.
Motilin stimulates motility (contraction) of GI smooth muscle and underlies the migrating motor
complex. In this connection, motilin does cause relaxation of the pylorus of the stomach
(allowing undigested matter to leave the stomach and enter the duodenum). However, the
mechanisSee slides: 11, 12, 28, 29 and 33 of General Principles lecture. For further reading see Chapter 26
of "Ganong's Review of Medical Physiology"m of this is unresolved.
8.
55‐year‐old man complains of producing excessive volumes of saliva following the fitting of a new denture to replace some of his teeth. Laboratory analysis of his saliva is likely to show which of the following characteristics?
Correct Answer
D. Potassium concentration higher than in plasma
Explanation
Salivary secretion is stimulated by a variety of physical and chemical stimuli stimuli in
the oral cavity. The ionic composition of saliva depends on the rate of production. Saliva is
formed in a "two stage" process which involves secretion of a plasma like solution by acinar cells.
As this acinar solution flows along the ducts, it is modifed by the transport activity of the ductal
cells (ductal modification). The modification is that sodium and chloride are reabsorbed, but
potassium and bicarbonate are secreted to concentrations higher than that in plasma.
The ducts have very low permeability to water, so as sodium and chloride absorption exceeds
the rate of potassium and bicarbonate secretion, the fluid is diluted, and saliva is always
hypotonic to plasma. As flow increases, the capacity of the ducts to absorb sodium and chloride
is reduced so the concentration of these ions increase towards but never reaching that of
plasma. On the other hand, the concentration of potassium and bicarbonate increase with flow,
because the rate of their secretion is increases with flow. The concentration of potassium and
bicarbonate are always above that in plasma.
See slides 17 & 19 of General Principles lecture. For further reading see Chapter 4 of
"Gastrointestinal Physiology"
9.
As part of a research project, contractile activity of smooth muscle (tension) and the rate of fluid secretion of a piece of human jejunum were monitored. A physiological dose of a gastrointestinal peptide was given. The rate of fluid secretion increased and the tension of the smooth muscle decreased. Which of the following peptides was the one most likely to have produced these effects?
Correct Answer
C. Vasoactive intestinal polypeptide (VIP)
Explanation
Vasoactive Intestinal Polypeptide is released from enteric neurons and is a potent
stimulator (secretagogue) of fluid secretion in the intestine (see slide 39 of small intestine
lecture), and also is an inhibitory neurotransmitter causing relaxation of smooth muscle
throughout the gastrointestinal system (slide 29 of General Principles lecture). Of the other
choices, none have significant effects on intestinal fluid secretion:
Cholecystokinin does have effects on smooth muscle contraction ‐ particularly of the gall
bladder but causes contraction. Motilin, stimulates gastrointestinal motility, GLP‐1 reduces
gastric motility, but not in physiological doses. Its major physiological role is to stimulate insulin
secretion from pancreatic beta cells. Gastrin increases gastric smooth muscle contraction ‐ but
its major role is in the control of acid secretion by parietal cells. (See slide 11 of General
principles lecture).
See Chapter 26 of "Ganong's Review of Medical Physiology" for further reading.
10.
10.
A 4‐year‐old girl is brought to the emergency room having swallowed one or two steel ball bearings of approximately a quarter of an inch (6 mm) in diameter. The parents are advised to return home and withhold food from their daughter for 12 hours, because the bearing will be eventually passed in her stools. What type of motility pattern is primarily responsible for the elimination of the ball bearings.
Correct Answer
D. Migrating Motor Complex
Explanation
In the inter‐meal (inter‐digestive period) the motility pattern of the GI tract is
dominated by the migrating motor complex (MMC). The MMC begins at around the time the
contents of the preceding meal has reached the cecum. The MMC is characterized by strong
peristaltic waves of contractions that occur every about every 90 ‐ 120 minutes. They arise in
the antral stomach and pass along the whole of the small intestine as far as the ileocecal valve.
The hormone that is involved with "setting the clock" of these contractions is motilin. Motilin
stimulates smooth muscle contractions in the antral stomach and small intestine, but relaxes the
pylorus. This relaxation, combined with the powerful contractions is usually sufficient to propel
a swallowed inert object such as a ball bearing into the small intestine. The object travels
through the small intestine into the large intestine and then is eliminated in the stools.
Antral systole is the contractions of the antral part of the stomach that underlie "retropulsion"‐
contractions of the stomach that force gastric contents against a closed pylorus ‐ helping to
break food (but not a ball bearing!) down to small enough particles (